Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-19T12:24:23.724Z Has data issue: false hasContentIssue false
  • English
  • Français

Ethical Considerations in Ending Exploratory Brain–Computer Interface Research Studies in Locked-in Syndrome

Published online by Cambridge University Press:  10 September 2018

ERAN KLEIN ,
BETTS PETERS  and
MATT HIGGER
Get access Rights & Permissions [Opens in a new window]

Abstract:

Brain–computer interface (BCI) is a promising technology for restoring communication in individuals with locked-in syndrome (LIS). BCI technology offers a potential tool for individuals with impaired or absent means of effective communication to use brain activity to control an output device such as a computer keyboard. Exploratory studies of BCI devices for communication in people with LIS are underway. Research with individuals with LIS presents not only technological challenges, but ethical challenges as well. Whereas recent attention has been focused on ethical issues that arise at the initiation of studies, such as how to obtain valid consent, relatively little attention has been given to issues at the conclusion of studies. BCI research in LIS highlights one such challenge: How to decide when an exploratory BCI research study should end. In this article, we present the case of an individual with presumed LIS enrolled in an exploratory BCI study. We consider whether two common ethical frameworks for stopping randomized clinical trials—equipoise and nonexploitation—can be usefully applied to elucidating researcher obligations to end exploratory BCI research. We argue that neither framework is a good fit for exploratory BCI research. Instead, we apply recent work on clinician-researcher fiduciary obligations and in turn offer some preliminary recommendations for BCI researchers on how to end exploratory BCI studies.

Keywords

Brain–computer interface (BCI)locked-in syndrome (LIS)exploratory researchrandomized clinical trials
Type
Articles
Information
Cambridge Quarterly of Healthcare Ethics , Volume 27 , Special Issue 4: Clinical Neuroethics , October 2018 , pp. 660 - 674
Copyright
Copyright © Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

We are grateful to the research participant pair who worked with us on this project. This work was funded by National Institutes of Health (NIH) grant #2R01DC009834-06A1, National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) grant #90RE5017, and NSF #EEC 1028725, and NIH-5T32MH016259-38.

References

Notes

1. For definitions of LIS, see Bauer, G, Gerstenbrand, F, Rumpl, E. Varieties of the locked-in syndrome. Journal of Neurology 1979;221(2):77–91CrossRefGoogle ScholarPubMed and Smith, E, Delargy, M. Locked-in syndrome. Clinical Review British Medical Journal 2005;330:406–9.CrossRefGoogle ScholarPubMed The difficulty of distinguishing total LIS from a disorder of consciousness (e.g., persistent vegetative state [PVS]) based on a criterion of observable behavior has led some to offer the term “functional LIS” or “behaviorally unresponsive” patients who retain residual covert awareness. See Bruno, MA, Vanhaudenhuyse, A, Thibaut, A, Moonen, G, Laureys, S. From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness. Journal of Neurology 2011;258(7):1373–84CrossRefGoogle ScholarPubMed and Peterson, A, Naci, L, Weijer, C, Cruse, D, Fernández-Espejo, D, Graham, M, et al. Assessing decision-making capacity in the behaviorally nonresponsive patient with residual covert awareness. AJOB Neuroscience 2013;4(4):3–14.CrossRefGoogle Scholar As will be noted in the case discussed here, we put this terminological debate to the side.

2. Chiò, A, Logroscino, G, Hardiman, O, Swingler, R, Mitchell, D, Beghi, E, et al. Eurals Consortium. Prognostic factors in ALS: A critical review. Amyotrophic Lateral Sclerosis 2009;10(5–6):310–23.CrossRefGoogle ScholarPubMed

3. See note 1, Smith 2005.

4. Vansteensel, MJ, Pels, EG, Bleichner, MG, Branco, MP, Denison, T, Freudenburg, ZV, et al. Fully implanted brain–computer interface in a locked-in patient with ALS. New England Journal of Medicine 2016;375(21):2060–6.CrossRefGoogle Scholar

5. Akcakaya, M, Peters, B, Moghadamfalahi, M, Mooney, AR, Orhan, U, Oken, B, et al. Noninvasive brain–computer interfaces for augmentative and alternative communication. IEEE Reviews in Biomedical Engineering 2014;7:31–49.CrossRefGoogle ScholarPubMed

6. Wolpaw, JR, Birbaumer, N, McFarland, DJ, Pfurtscheller, G, Vaughan, TM. Brain–computer interfaces for communication and control. Clinical Neurophysiology 2002;113(6):767–91;CrossRefGoogle ScholarPubMed Blankertz, B, Dornhege, G, Krauledat, M, Schröder, M, Williamson, J, Murray-Smith, R, et al. The Berlin brain–computer interface presents the novel mental typewriter Hex-o-Spell. In: Proceedings of the 3rd International Brain–Computer Interface Workshop and Training Course, September 21–24 2006.Google Scholar Graz:Verlag der Technischen Universität Graz 2006; available at http://eprints.maynoothuniversity.ie/1786/ (last accessed 15 May 2018).Google Scholar

7. Haselager, P, Vlek, R, Hill, J, Nijboer, F. A note on ethical aspects of BCI. Neural Networks 2009; 22(9):1352–7;CrossRefGoogle ScholarPubMed Clausen, J. Conceptual and ethical issues with brain–hardware interfaces. Current Opinion in Psychiatry 2011;24(6):495–501.CrossRefGoogle ScholarPubMed

8. Phillips, LH. Communicating with the “locked-in” patient: Because you can do it, should you? Neurology 2006;67(3):380–1.CrossRefGoogle Scholar

9. Bruno, MA, Bernheim, JL, Ledoux, D, Pellas, F, Demertzi, A, Laureys, S. A survey on self-assessed well-being in a cohort of chronic locked-in syndrome patients: happy majority, miserable minority. BMJ Open. 2011;1(1):e000039;CrossRefGoogle Scholar Laureys, S, Pellas, F, Van Eeckhout, P, Ghorbel, S, Schnakers, C, Perrin, F, et al. The locked-in syndrome: What is it like to be conscious but paralyzed and voiceless? Progress in Brain Research 2005;150:495–611.CrossRefGoogle ScholarPubMed

10. See note 7, Clausen 2011.

11. Kyselo, M. Locked-in syndrome and BCI—towards an enactive approach to the self. Neuroethics 2013;6(3):579–91.CrossRefGoogle Scholar

12. Johansson, V, Soekadar, SR, Clausen, J. Locked out: Ignorance and responsibility in brain–computer interface communication in locked-in syndrome. Cambridge Quarterly of Healthcare Ethics. 2017;26(4):555–76.CrossRefGoogle Scholar

13. Kageyama, Y, Hirata, M, Yanagisawa, T, Shimokawa, T, Sawada, J, Morris, S, et al. Severely affected ALS patients have broad and high expectations for brain–machine interfaces. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2014;15(7–8):513–9.CrossRefGoogle ScholarPubMed

14. United States National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Guidelines for the Protection of Human Subjects of Research. Washington, DC: United States Government Printing Office; 1979.Google Scholar

15. Bendtsen, K. Communicating with the minimally conscious: Ethical implications in end-of-life care. AJOB Neuroscience 2013;4(1):46–51;CrossRefGoogle Scholar Monti, MM, Vanhaudenhuyse, A, Coleman, MR, Boly, M, Pickard, JD, Tshibanda, L, et al. Willful modulation of brain activity in disorders of consciousness. New England Journal of Medicine 2010;362(7):579–89;CrossRefGoogle ScholarPubMed Fins, JJ. A proposed ethical framework for interventional cognitive neuroscience: A consideration of deep brain stimulation impaired consciousness. Neurological Research. 2000;22(3):273–8.CrossRefGoogle ScholarPubMed

16. We mean to distinguish exploratory research in a general sense from regulatory definitions of exploratory research, such as the United States Food And Drug Administration’s (FDA) use of exploratory research to connote an investigational drug trial that “(1) is conducted early in phase 1; (2) involves very limited human exposure; and (3) has no therapeutic or diagnostic intent.” See Guidance for industry, investigators, and reviewers on exploratory IND studies. FDA, January 2006; available at https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm078933.pdf (last accessed 11 May 2018).

17. We have elected not to use the participant’s real name because we are unable to obtain his consent for this. His wife, his surrogate decisionmaker, gave permission to discuss this case and their involvement in this research project.

18. We appreciate that for those who adopt a strict definition of BCI research—namely, that BCI research uses neural data exclusively—the current study may fail to meet this definition. EMG and EOG are often equally encouraging directions of research. EMG measures muscle activity via electrodes placed on the surface of the skin, whereas EOG is a special type of EMG that relates to eye movement. In this article, we take the more inclusive view that a BCI study can include both neural data and non-neural data (EOG, EMG, eye gaze).

19. Higger, M, Quivira, F, Akcakaya, M, Moghadamfalahi, M, Nezamfar, H, Cetin, M, et al. Recursive Bayesian coding for BCIs. IEEE Transactions on Neural Systems and Rehabilitation Engineering 2017;25:704–14.CrossRefGoogle ScholarPubMed

20. Fried, C. Medical Experimentation: Personal Integrity and Social Policy. New York: American Elsevier; 1974.Google Scholar

21. Freedman, B. Equipoise and the ethics of clinical research. New England Journal of Medicine 1987; 317(3):141–5;CrossRefGoogle ScholarPubMed Djulbegovic, B. Articulating and responding to uncertainties in clinical research. Journal of Medicine and Philosophy 2007;32(2):79–98;CrossRefGoogle ScholarPubMed Veatch, RM. Indifference of subjects: An alternative to equipoise in randomized clinical trials. Social Philosophy and Policy 2002;19(2):295–323;CrossRefGoogle ScholarPubMed Ashcroft, R. Equipoise, knowledge and ethics in clinical research and practice. Bioethics 1999;13(3–4):314–26;CrossRefGoogle ScholarPubMed Buchanan, D, Miller, FG. Principles of early stopping of randomized trials for efficacy: A critique of equipoise and an alternative nonexploitation ethical framework. Kennedy Institute of Ethics Journal 2005;15(2):161–78;CrossRefGoogle ScholarPubMed Miller, FG, Joffe, S. Equipoise and the dilemma of randomized clinical trials. New England Journal of Medicine 2011;364(5):476–80;CrossRefGoogle ScholarPubMed London, AJ. Clinical equipoise: Foundational requirement or fundamental error? In: Steinbock, B, ed, The Oxford Handbook of Bioethics. New York: Oxford University Press; 2009:571–96;Google Scholar Gifford, F. Community-equipoise and the ethics of randomized clinical trials. Bioethics 1995;9(2):127–48;CrossRefGoogle ScholarPubMed Karlawish, JH, Lantos, J. Community equipoise and the architecture of clinical research. Cambridge Quarterly of Healthcare Ethics 1997;6(4):385–96;CrossRefGoogle ScholarPubMed Weijer, C, Shapiro, SH, Cranley, KG. For and against: Clinical equipoise and not the uncertainty principle is the moral underpinning of the randomised controlled trial. BMJ (Clinical Research ed.). 2000; 321(7263):756–8;CrossRefGoogle Scholar Chiong, W. The real problem with equipoise. The American Journal of Bioethics 2006;6(4):37–47.CrossRefGoogle ScholarPubMed

22. Deng, C, Hanna, K, Bril, V, Dalakas, MC, Donofrio, P, van Doorn, PA, et al. Challenges of clinical trial design when there is lack of clinical equipoise: Use of a response-conditional crossover design. Journal of Neurology 2012;259(2):348–52.CrossRefGoogle ScholarPubMed

23. Ghogawala, Z, Barker, FG, Carter, BS. Clinical equipoise and the surgical randomized controlled trial. Neurosurgery 2008;62(6):N9–10.CrossRefGoogle Scholar

24. Wasiewski, WW, Johnston, KC. Clinical trials, devices, unproven treatments, and clinical equipoise. Stroke 2009;40(6):e441–2;CrossRefGoogle ScholarPubMed McGirr, A, Mohammed, S, Kurlan, R, Cusimano, MD. Clinical equipoise in idiopathic normal pressure hydrocephalus: A survey of physicians on the need for randomized controlled trials assessing the efficacy of cerebrospinal fluid diversion. Journal of the Neurological Sciences 2013;333(1):13–8.CrossRefGoogle ScholarPubMed

25. González-Lara, LE, Owen, AM. Identifying covert cognition in disorders of consciousness. In: Coma and Disorders of Consciousness, Springer. 2017; 77–96; available at https://link.springer.com/chapter/10.1007/978-3-319-55964-3_5 (last accessed 11 May 2018).Google Scholar

26. See note 21, London 2009.

27. Miller, FG, Brody, H. A critique of clinical equipoise:Ttherapeutic misconception in the ethics of clinical trials. Hastings Center Report 2003;33(3):19–28.CrossRefGoogle Scholar

28. OCEBM Levels of Evidence Working Group “The Oxford 2011 Levels of Evidence.” Oxford Centre for Evidence-Based Medicine; available at http://www.cebm.net/index.aspx?o=5653 (last accessed 27 Feb 2018).Google Scholar

29. See note 21, Buchanan, Miller 2005.

30. Kübler, A, Winter, S, Ludolph, AC, Hautzinger, M, Birbaumer, N. Severity of depressive symptoms and quality of life in patients with amyotrophic lateral sclerosis. Neurorehabilitation and Neural Repair 2005;19(3):182–93.CrossRefGoogle ScholarPubMed

31. Herron, JA, Thompson, MC, Brown, T, Chizeck, HJ, Ojemann, JG, Ko, AL. Chronic electrocorticography for sensing movement intention and closed-loop deep brain stimulation with wearable sensors in an essential tremor patient. Journal of Neurosurgery 2016;127(3):580–7.Google Scholar

32. Hochberg, LR, Serruya, MD, Friehs, GM, Mukand, JA, Saleh, M, Caplan, AH, et al. Neuronal ensemble control of prosthetic devices by a human with tetraplegia. Nature 2006;442(7099):164–71.CrossRefGoogle ScholarPubMed

33. Miller, PB, Weijer, C. Rehabilitating equipoise. Kennedy Institute of Ethics Journal 2003;13(2):93–118;CrossRefGoogle ScholarPubMed Miller, PB, Weijer, C. Trust based obligations of the state and physician-researchers to patient-subjects. Journal of Medical Ethics 2006a;32(9):542–7;CrossRefGoogle Scholar Miller, PB, Weijer, C. Fiduciary obligation in clinical research. The Journal of Law, Medicine & Ethics 2006b;34(2):424–40.CrossRefGoogle Scholar

34. Questions were read aloud to the participant (and repeated several times), but the researchers did not elicit reliable verbal or motor responses. The participant’s wife felt that he did respond affirmatively to some of these questions through eye movements, but researchers were unable to confirm these. The participant’s wife provided surrogate consent for research participation.

35. Vlek, RJ, Steines, D, Szibbo, D, Kübler, A, Schneider, MJ, Haselager, P, et al. Ethical issues in brain–computer interface research, development, and dissemination. Journal of Neurologic Physical Therapy 2012;36(2):94–9.CrossRefGoogle ScholarPubMed

36. Grübler, G, Al-Khodairy, A, Leeb, R, Pisotta, I, Riccio, A, Rohm, M, et al. Psychosocial and ethical aspects in non-invasive EEG-based BCI research—A survey among BCI users and BCI professionals. Neuroethics 2014;7(1):29–41, at 35.CrossRefGoogle Scholar

37. Appelbaum, PS, Roth, LH, Lidz, CW, Benson, P, Winslade, W. False hopes and best data: Consent to research and the therapeutic misconception. Hastings Center Report 1987;17(2):20–4.CrossRefGoogle ScholarPubMed

38. Sulmasy, DP, Astrow, AB, He, MK, Seils, DM, Meropol, NJ, Micco, E, et al. The culture of faith and hope: Patients’ justifications for their high estimations of expected therapeutic benefit when enrolling in early phase oncology trials. Cancer 2010;116(15):3702–11;CrossRefGoogle ScholarPubMed Weinfurt, KP, Castel, LD, Li, Y, Sulmasy, DP, Balshem, AM, Benson, AB, et al. The correlation between patient characteristics and expectations of benefit from Phase I clinical trials. Cancer 2003;98(1):166–75.CrossRefGoogle ScholarPubMed

39. Lipsman, N, Giacobbe, P, Bernstein, M, Lozano, AM. Informed consent for clinical trials of deep brain stimulation in psychiatric disease: challenges and implications for trial design. Journal of Medical Ethics. 2012;38(2):107–11.CrossRefGoogle ScholarPubMed

40. Edwards, SJ. Protecting privacy interests in brain images: The limits of consent. In: I Know What You’re Thinking. Brain Imaging and Mental Privacy. Oxford: Oxford University Press; 2012:245–60.CrossRefGoogle Scholar

41. See note 35, Vlek et al. 2012.

42. See note 36, Grübler et al. 2014.

43. See note 33, Miller, Weijer 2006a, 2006b.

44. See note 27, Miller, Brody 2003.

45. See note 33, Miller, Weijer 2006a, 2006b.

46. See note 21, London 2009, Chiong 2006.

47. Anderson, JA. Contextualizing clinical research: The epistemological role of clinical equipoise. Theoretical Medicine and Bioethics 2009;30(4):269–88;CrossRefGoogle ScholarPubMed Anderson, JA. Clinical research in context: Reexamining the distinction between research and practice. Journal of Medicine and Philosophy 2010;35(1):46–63.CrossRefGoogle ScholarPubMed

48. Kowalski, CJ, Hutchinson, RJ, Mrdjenovich, AJ. The ethics of clinical care and the ethics of clinical research: Yin and yang. The Journal of Medicine and Philosophy 2017;42(1):7–32.CrossRefGoogle ScholarPubMed

49. Hess, P. Intracranial stem cell-based transplantation: Reconsidering the ethics of phase 1 clinical trials in light of irreversible interventions in the brain. AJOB Neuroscience 2012;3(2):3–13.CrossRefGoogle Scholar

50. Clarification of roles may require concomitant development of new terminology to label these roles. For example, the terms “team” and “team members” are ambiguous as to whether participants and caregivers are encompassed by these terms. Additional terminology may need to be adopted (e.g., the “researcher team,” which is subject to regulatory oversight versus the broader “project team,” which also includes research participants and caregivers). To avoid confusion in describing the current study, we have kept, somewhat reluctantly, to the convention of using “team” to only refer to traditional researchers (not the participant and family), in the case described here, a speech-language pathologist and two engineers.